Diabetic bladder dysfunction (DBD) refers to a spectrum of urinary bladder symptoms that manifest in the majority of people with diabetes mellitus. Secondary sequelae of DBD are often health-compromising, and diminished bladder control markedly reduces quality of life. Like its phenotype, the pathogenesis of DBD is multifaceted. Changes in the autonomic nervous system and detrusor that contribute to DBD are well described; however, there is suggestive evidence that the peripheral nervous system is part of the pathogenesis. It is clearly evident from diabetic cutaneous neuropathy that sensory neural changes do occur, and the contribution of those changes to the development and progression of DBD merit more attention. With an overarching goal of identifying therapeutic targets to treat or prevent diabetes-induced changes in bladder-innervating PANs that play a role in DBD, we propose to characterize their functional, neurochemical, and genetic changes in an animal model of diabetes. In parallel, we will examine peripheral nerve changes in bladder tissue from individuals with a history of diabetes who present with DBD to inform the translational relevance of our animal model findings. Objective, clinical evidence of neuropathic bladder dysfunction in diabetic individuals who self-report being ?asymptomatic? has suggested there is a high frequency of subclinical diabetic neuropathy. Development of cystopathy may be prevented in those with subclinical neuropathy by targeted intervention, potential targets of which we hope to identify. In turn, this could mitigate numerous secondary sequelae that cost money and impair quality of life.
Urinary bladder dysfunction affects the majority of people with diabetes mellitus and negatively impacts health and quality of life. This study will examine the role of peripheral sensory nerves in the pathogenesis of diabetic bladder dysfunction using an animal model and human tissues. The findings of this study may identify novel therapeutic targets for clinical intervention and will enhance translational bladder sensory neurobiology science. !
